NEW findings from the COVAIL trial provide insights into how neutralising antibody titers correlate with protection against COVID-19, particularly following a second mRNA booster. The study evaluates the effectiveness of bivalent and monovalent vaccine boosters containing Spike proteins from various SARS-CoV-2 variants, including Omicron, Beta, and Delta.
The trial involved 985 participants who received boosters during the Omicron BA.2-BA.5-dominant period. Researchers measured neutralising antibody titers against five SARS-CoV-2 strains to assess their relationship with symptomatic COVID-19 risk over six months. The results showed that higher neutralising antibody titers were consistently linked to lower COVID-19 risk across all vaccine types and Spike inserts. However, the protective effects of neutralising antibodies were notably stronger in individuals with prior SARS-CoV-2 infection compared to those who were infection-naïve.
For individuals without prior infection, the reduction in COVID-19 risk per tenfold increase in neutralising antibody titer was smaller [hazard ratio 0.74 (95% CI 0.59–0.94)] compared to those with prior infection [hazard ratio 0.41 (95% CI 0.23–0.64)]. This finding raises important questions about how previous infection modulates the immune response to subsequent vaccinations.
Lead researchers noted that while neutralising antibody titers remain a critical correlate of vaccine efficacy, their predictive strength varies based on prior infection history. “This study underscores the need for nuanced approaches to evaluating vaccine performance, especially as variant-adapted boosters become more widely used,” they stated.
The study also highlighted the durable inverse correlation between neutralising titers and Omicron infection risk, further supporting the role of boosters in enhancing immunity, particularly for individuals with prior exposure to the virus.
These findings contribute to the ongoing discussion about optimising vaccine strategies in a landscape of evolving variants and differing individual immune histories.
Aleksandra Zurowska, EMJ
Reference
Zhang B et al. Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost. Nat Commun. 2025;DOI:10.1038/s41467-025-55931-w.
